Tumor associated monoclonal antibodies (mAb) are potential therapeutic agents as selective carriers of cytotoxic agents to malignant cells. This hypothesis is tested in animal model systems with mAbs directed toward antigens associated with a variety of malignancies. The cytocidal agents being employed are various radionuclides. Their relative efficacy when conjugated to monoclonal antibodies (mAbs) is assayed and compared to that of mAbs alone, radiolabeled with I-131, or conjugated to toxins. The radionuclides chosen for study span the range of radionuclidic properties available thereby assaying the effects of energy of emission, half-life, and physical characteristics of emission. Research continues to focus on expanding clinical use of Y-90 and on completing pre-clinical studies with the alpha-particle emitting radionuclides Bi-212, Bi-213, and At-211. Ongoing clinical trials currently employ the second generation bifunctional chelating agent 1B4M-DTPA (aka MX-DTPA) for sequestering Y-90 and future trials being planned will use the CHX-A DTPA. Recent results in chelate design technology have yielded new ligands for Pb(II) isotopes (TCMC), and HEHA, currently the only ligand that forms a complex with Ac-225 that demonstrates stability in vivo to data. Efforts at evaluating the bifunctional versions of each are ongoing in the appropriate murine model systems. Current pre-clinical results with the alpha emitter Bi- 213 with the humanized CH2 domain deleted engineered antibody CC49 has generated remarkable results. Contrary to the conventional paradygm that established tumors can not be treated with an alpha emitter radioimmunoconjugate, ~60% of mice treated with a 750 microcurie dose either produced a partial respose wherein the tumor growth was arrested or a complete response wherein the tumor was essentially eradicated. However, regardless of dose, ~30% treated failed to respond positively. This series of experiments continues to be expanded to a larger population and slightly increased doses. In parallel, use of the in vivo generator system of Pb-212/Bi-212 in the same murine system is planned in provide both a greater dose and an enhanced half-life to improve targeting pharmacokinetics. - imaging, metal chelates, monoclonal antibodies, radiation, radioimmunotherapy,